Cyclophosphamide and Fludarabine Followed by Vaccine Therapy, Gene-Modified White Blood Cell Infusions, and Aldesleukin in Treating Patients With Metastatic Melanoma

NCT00091104 | Completed Phase 1

• 4 other identifiers: 04025104-C-0251NCI-6974CDR0000383246
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Inserting a laboratory-treated gene into a person's white blood cells may make the body build an immune response to kill tumor cells. Giving cyclophosphamide and fludarabine before a white blood cell infusion may suppress the immune system and allow tumor cells to be killed. Vaccines may make the body build an immune response to kill tumor cells. Aldesleukin may stimulate a person's white blood cells to kill tumor cells. Combining white blood cell infusion with vaccine therapy and aldesleukin may cause a stronger immune response and kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of gene-modified white blood cells when given together with cyclophosphamide, fludarabine, vaccine therapy, and aldesleukin and to see how well it works in treating patients with metastatic melanoma.

Conditions

Melanoma (Skin)

Keywords

stage IV melanoma; recurrent melanoma

Outcome Measures

Primary Outcomes (2)

• Safety

• Tumor regression

Secondary Outcomes (2)

• In vivo survival of transplanted cells

• Clinical response

Interventions

MART-1:27-35 peptide vaccine BIOLOGICAL

aldesleukin BIOLOGICAL

filgrastim BIOLOGICAL

incomplete Freund's adjuvant BIOLOGICAL

therapeutic autologous lymphocytes BIOLOGICAL

therapeutic tumor infiltrating lymphocytes BIOLOGICAL

cyclophosphamide DRUG

fludarabine phosphate DRUG

autologous hematopoietic stem cell transplantation PROCEDURE

in vitro-treated peripheral blood stem cell transplantation PROCEDURE

total-body irradiation RADIATION

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of metastatic melanoma * HLA-A\*0201-positive disease * Measurable disease * Refractory to standard therapy, including high-dose aldesleukin therapy PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-1 Life expectancy * More than 3 months Hematopoietic * Absolute neutrophil count \> 1,000/mm\^3 * Platelet count \> 100,000/mm\^3 * Hemoglobin \> 8.0 g/dL * Lymphocyte count \> 500/mm\^3 * WBC \> 3,000/mm\^3 * No coagulation disorder Hepatic * ALT and AST \< 3 times upper limit of normal * Bilirubin ≤ 2.0 mg/dL (\< 3.0 mg/dL for patients with Gilbert's disease) * Hepatitis B antigen negative * Hepatitis C antibody negative (unless antigen negative) Renal * Creatinine ≤ 1.6 mg/dL Cardiovascular * No myocardial infarction * No cardiac arrhythmias * No cardiac ischemia * LVEF ≥ 45% by stress cardiac test\* (for patients ≥ 50 years of age OR those with a history of EKG abnormalities) * No other major cardiovascular illness by stress thallium or comparable test NOTE: \*Stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test Pulmonary * No major respiratory illness * No obstructive or restrictive pulmonary disease * FEV\_1 ≥ 60% of predicted on pulmonary function test\* * DLCO ≥ 60% predicted (for total-body irradiation cohort) NOTE: \*For patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction Immunologic * HIV negative * No major immune system illness * No active systemic infection or opportunistic infection * No primary immunodeficiency (e.g., autoimmune colitis or Crohn's disease) * No secondary immunodeficiency (e.g., due to chemotherapy or radiotherapy) * No history of severe immediate hypersensitivity reaction to study drugs Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 4 months after completion of study treatment * Must sign a durable power of attorney PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * Recovered from prior immunotherapy * Prior immunization to melanoma antigens allowed * Progressive disease during prior immunization allowed * Prior cellular therapy, including vector transduction with or without myeloablation, allowed * More than 6 weeks since prior anticytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibody (MDX-010) therapy * No prior anti-CTLA-4 antibody unless a post anti-CTLA-4 antibody treatment colonoscopy was normal by biopsy Chemotherapy * Recovered from prior chemotherapy Endocrine therapy * No concurrent systemic steroids Radiotherapy * Recovered from prior radiotherapy * No prior significant mediastinal or lung radiation (for total-body irradiation cohort) Surgery * Not specified Other * More than 4 weeks since prior systemic therapy and recovered

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

NCI - Surgery Branch

Bethesda, Maryland, 20892-1201, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

aldesleukin; Filgrastim; incomplete Freund's adjuvant; Cyclophosphamide; fludarabine phosphate; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques

Study Officials

• Steven A. Rosenberg, MD, PhD

  NCI - Surgery Branch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: September 7, 2004
• First Posted: September 8, 2004
• Study Start: July 1, 2004
• Primary Completion: August 1, 2010
• Study Completion: October 1, 2010
• Last Updated: March 15, 2012

Record last verified: 2012-03

Locations

US (2)